Immunity, inflammation and reservoir in patients at an early stage of HIV infection on intermittent ART (ANRS 141 TIPI Trial)
Lionel Piroth
(1, 2)
,
Laetitia Moinot
(3)
,
Patrick Yeni
(4)
,
Véronique Avettand-Fénoel
(5)
,
Jacques Reynes
(6)
,
Pierre-Marie Girard
(7)
,
Bruno Marchou
(8)
,
Aurore Georget
(3)
,
Christine Rouzioux
(9, 10)
,
Brigitte Autran
(11)
,
Laurence Duvillard
(12, 13)
,
Geneviève Chêne
(3)
,
Catherine Fagard
(3)
1
CHU Dijon
2 Agroécologie [Dijon]
3 Epidémiologie et Biostatistique [Bordeaux]
4 Hôpital Bichat - Claude Bernard
5 EA 7327 - Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV)
6 TransVIHMI - Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes
7 CHU Saint-Antoine [AP-HP]
8 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
9 Laboratoire de Microbiologie Clinique [AP-HP Hôpital Necker-Enfants Malades]
10 Laboratoire de Virologie [CHU Necker]
11 CHU Pitié-Salpêtrière [AP-HP]
12 LNC - Lipides - Nutrition - Cancer (U866)
13 Laboratoire de biochimie médicale (CHU de Dijon)
2 Agroécologie [Dijon]
3 Epidémiologie et Biostatistique [Bordeaux]
4 Hôpital Bichat - Claude Bernard
5 EA 7327 - Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV)
6 TransVIHMI - Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes
7 CHU Saint-Antoine [AP-HP]
8 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
9 Laboratoire de Microbiologie Clinique [AP-HP Hôpital Necker-Enfants Malades]
10 Laboratoire de Virologie [CHU Necker]
11 CHU Pitié-Salpêtrière [AP-HP]
12 LNC - Lipides - Nutrition - Cancer (U866)
13 Laboratoire de biochimie médicale (CHU de Dijon)
Lionel Piroth
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- PersonId : 1136581
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Bruno Marchou
- Fonction : Auteur
- PersonId : 900564
- ORCID : 0000-0002-0673-2945
Laurence Duvillard
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- PersonId : 1217418
- ORCID : 0000-0001-9320-793X
- IdRef : 16490980X
Résumé
The objective of this study was to assess clinical and biological changes during intermittent ART (I-ART) started early, with significant time spent on versus off ART, which has never before been studied in ART-naive patients with high nadir and current CD4 cell count.
ART-naive HIV-1-infected patients with baseline CD4 a parts per thousand yen500/mm(3) and nadir CD4 a parts per thousand yen400/mm(3) received 2 years of I-ART (6 month periods on once-daily boosted-PI-based ART, alternating with 6 month periods without ART) in a 2 year, Phase II, non-comparative multicentre trial. The trial is registered with ClinicalTrials.gov, number NCT 00820118.
The CD4 cell count remained a parts per thousand yen500/mm(3) at 2 years in all 44 patients included in the study. The mean 2 year count was higher than the mean count at baseline in 24 patients overall (55%; 95% CI 40%-69%) and in 20 (65%; 95% CI 48%-81%) of the 31 patients who fully adhered to the trial strategy. All but three of these latter patients had HIV-1 RNA concentrations below 50 copies/mL after each 6 month 'on' period. Only one strategy-related genotypic mutation (M184I) was detected. The HIV-1 DNA median load fluctuated, but it did not differ between month 0 and month 24 (2.8 versus 2.6 log(10) copies/10(6) leucocytes, PaEuroS=aEuroS0.29). Biomarkers of inflammation and endothelial activation remained stable between month 0 and month 24. Naive CD4, CD8+CCR5+ and CD8+CD38+ T cell numbers tended to decline. One patient developed Burkitt's lymphoma and 12 patients reported sexually transmitted infections.
In patients with high nadir and current CD4 cell counts, 2 year I-ART maintained the CD4 cell count above 500/mm(3), with no increase in the viral reservoir. Immune activation seems related to HIV replication, while inflammation seems to evolve independently and require specific attention.
Domaines
Maladies infectieusesFormat du dépôt | Notice |
---|---|
Type de dépôt | Article dans une revue |
Titre |
en
Immunity, inflammation and reservoir in patients at an early stage of HIV infection on intermittent ART (ANRS 141 TIPI Trial)
|
Résumé |
en
The objective of this study was to assess clinical and biological changes during intermittent ART (I-ART) started early, with significant time spent on versus off ART, which has never before been studied in ART-naive patients with high nadir and current CD4 cell count.
ART-naive HIV-1-infected patients with baseline CD4 a parts per thousand yen500/mm(3) and nadir CD4 a parts per thousand yen400/mm(3) received 2 years of I-ART (6 month periods on once-daily boosted-PI-based ART, alternating with 6 month periods without ART) in a 2 year, Phase II, non-comparative multicentre trial. The trial is registered with ClinicalTrials.gov, number NCT 00820118.
The CD4 cell count remained a parts per thousand yen500/mm(3) at 2 years in all 44 patients included in the study. The mean 2 year count was higher than the mean count at baseline in 24 patients overall (55%; 95% CI 40%-69%) and in 20 (65%; 95% CI 48%-81%) of the 31 patients who fully adhered to the trial strategy. All but three of these latter patients had HIV-1 RNA concentrations below 50 copies/mL after each 6 month 'on' period. Only one strategy-related genotypic mutation (M184I) was detected. The HIV-1 DNA median load fluctuated, but it did not differ between month 0 and month 24 (2.8 versus 2.6 log(10) copies/10(6) leucocytes, PaEuroS=aEuroS0.29). Biomarkers of inflammation and endothelial activation remained stable between month 0 and month 24. Naive CD4, CD8+CCR5+ and CD8+CD38+ T cell numbers tended to decline. One patient developed Burkitt's lymphoma and 12 patients reported sexually transmitted infections.
In patients with high nadir and current CD4 cell counts, 2 year I-ART maintained the CD4 cell count above 500/mm(3), with no increase in the viral reservoir. Immune activation seems related to HIV replication, while inflammation seems to evolve independently and require specific attention.
|
Auteur(s) |
Lionel Piroth
1, 2
, Laetitia Moinot
3
, Patrick Yeni
4
, Véronique Avettand-Fénoel
5
, Jacques Reynes
6
, Pierre-Marie Girard
7
, Bruno Marchou
8
, Aurore Georget
3
, Christine Rouzioux
9, 10
, Brigitte Autran
11
, Laurence Duvillard
12, 13
, Geneviève Chêne
3
, Catherine Fagard
3
1
CHU Dijon
( 35051 )
- BP1542, 21034 Dijon cedex
- France
2
Agroécologie [Dijon]
( 183071 )
- Université de Bourgogne - 17 rue Sully - BP 86510 - 21000 Dijon
- France
3
Epidémiologie et Biostatistique [Bordeaux]
( 55677 )
- 146, rue Léo-Saignat 33076 Bordeaux
- France
4
Hôpital Bichat - Claude Bernard
( 26728 )
- 46, rue Henri-Huchard 75018 Paris
- France
5
EA 7327 -
Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV)
( 413087 )
- Faculté de médecine Site Necker - 156 Rue de Vaugirard 75730 Paris Cedex 15 / CHU Necker - 149 rue de Sèvres 75015 Paris
- France
6
TransVIHMI -
Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes
( 1087128 )
- Centre IRD France Sud 911, avenue Agropolis BP 64501 F-34394 Montpellier cedex 5
- France
7
CHU Saint-Antoine [AP-HP]
( 454982 )
- 184, rue du Faubourg Saint-Antoine
75571 Paris cedex 12
- France
8
CHU Toulouse -
Centre Hospitalier Universitaire de Toulouse
( 300075 )
- regroupe les hôpitaux Purpan, Rangueil, Pierre-Paul Riquet, Larey, Paule de Viguier, Hôtel Dieu Saint-Jacques, La Grave, etc.
- France
9
Laboratoire de Microbiologie Clinique [AP-HP Hôpital Necker-Enfants Malades]
( 487749 )
- France
10
Laboratoire de Virologie [CHU Necker]
( 59545 )
- 149, rue de Sèvres 75743 PARIS Cedex 15
- France
11
CHU Pitié-Salpêtrière [AP-HP]
( 353778 )
- 47-83 Boulevard de l'Hôpital, 75013 Paris
- France
12
LNC -
Lipides - Nutrition - Cancer (U866)
( 27738 )
- Université de Bourgogne - Faculte de medecine - 7, boulevard Jeanne d'Arc - BP 87900 - 21079 Dijon Cedex
- France
13
Laboratoire de biochimie médicale (CHU de Dijon)
( 477732 )
- CHU de Dijon - 14 rue Paul Gaffarel - 21079 Dijon
- France
|
Langue du document |
Anglais
|
Nom de la revue |
|
Vulgarisation |
Non
|
Comité de lecture |
Oui
|
Audience |
Internationale
|
Date de publication |
2016-02
|
Date de publication électronique |
2015-10-10
|
Volume |
71
|
Numéro |
2
|
Page/Identifiant |
490 - 496
|
Domaine(s) |
|
Mots-clés |
en
Antiretroviral Therapy, Highly Active/methods, CD4 Lymphocyte Count, HIV Infections/drug therapy, HIV Infections/immunology, HIV Infections/virology, HIV-1/immunology, HIV-1/isolation & purification, Inflammation/pathology, Viral Load
|
DOI | 10.1093/jac/dkv369 |
Pubmed Id | 26306824 |
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